The continuing aim of our research program is to define the mechanisms by which the ovarian steroids, especially progesterone, regulate the hypothalamic-pituitary-ovarian axis. This renewal is designed to examine especially the biochemistry and molecular basis of the effects of progesterone and some of its metabolites on pituitary and hypothalamic progesterone-sensitive processes such as gonadotropin and LHRH regulation. Specifically, we hope to elucidate: 1) the characteristics of progestin metabolism in hypothalamic and anterior pituitary tissues and its importance as a regulatory mechanism by examining the nature of the metabolites formed, the properties of the enzymes catalyzing these progestin steroid transformations and the regulation of the metabolism and enzymes, 2) the nature of the sequestered and reacting steroidal compounds; target tissue sites of localization and the mechanisms for sequestering and action at cellular and subcellular levels, 3) the biological relevance of metabolism to progesterone's effects on gonadotropin and LHRH regulation. The information gained is expected to give new insights into the steroidal regulatory mechanisms affecting the hypothalamic-ovarian axis, which might ultimately provide important information on the biomedical aspects of contraception and reveal new avenues for the control of fertility.